Here’s the conundrum: As every manufacturing manager knows, offering flexibility can be expensive. To design and build a facility that can accommodate any product, using all available technology, would be cost prohibitive. The capital required to “be all things to all products” would make a facility expensive, unwieldy and inefficient. Therefore, manufacturers of biopharmaceuticals have moved to common platforms, with industry-standard choices such as expression systems, standard unit operations, and even final product container/closure systems. Throughout the value chain of biopharma production, standardization has become the goal. On the surface, this standardization leads to efficiency. Regulatory agencies have become accustomed to seeing certain consistent technologies, resulting in reduced regulatory risk. A proven technology enables a manufacturer to move quickly, minimize investment in unproven compounds in development, and maximize the utilization of facilities.
However, anyone who has developed or implemented processes in multiple organizations knows that the concept of a “standard platform” is relative. As in many things, the devil is in the details: equipment choices and specifications, raw materials and consumables, and even the understanding of what is acceptable, and what is not acceptable, changes from organization to organization. The efficiency that is gained when a biopharma company has standardized its processes down to the final buffer can be lost when the process undergoes tech transfer. In fact, the highly prescriptive reliance on being true to a platform in every detail can often lead to significant inefficiencies. For instance, if a critical raw material is difficult to obtain, or a proprietary media formulation must be accessed from a vendor, this one fact could lead to delays and incur greater expense. Furthermore, the lack of standardization of product offerings from vendors can result in a reluctance to change. How many organizations are willing to try a different container/closure system after years of real-time stability data?
Biopharma Company Perspective
If you are seeking to outsource some, or all, of your production, you may (or may not) have established a platform system for production of your products. If you have a platform system, then the barriers to change can be significant, and the pressure to conform to this platform can be extremely high. If you can run your process at a CMO exactly as it was run in the past, and exactly as you wish it to be run in the future, your job is much easier. Your regulatory burden is lower, as you will have much less information to provide regulators during the site change. In addition, you have a very high chance of success under controlled conditions; by controlling change, you have controlled your risk. Given the inherent risks in drug development in general, every risk parameter you control is one less headache in the future. So you really want to run the process at the CMO exactly as it would run “at home.”
While I was with a biopharma firm, my management colleagues and I always looked for any possible opportunities to standardize processes. By doing this, we used fewer resources to develop a platform process, it took less time, and it enabled us to handle a much larger portfolio of projects. We standardized vendors, materials, methods, and anything else we could find. The key drive was to have as little product-specific effort expended as possible.
CMO Perspective
When you are working for the CMO, you can’t anticipate all possibilities when you design your facility and your processes. As mentioned above, offering greater flexibility can be expensive. Having every possible piece of equipment, and every possible component or consumable at your fingertips would be very difficult and inefficient. You have to anticipate the majority of your clients’ needs, and, applying the 80:20 Rule, try to cover 80% of the possibilities. Ideally, you have most of the equipment and materials that a client may need, and you have a well-prepared supply-chain group to procure those things that are not readily at hand. Achieving this can even be challenging, if you are working with evolving technologies that have yet to be standardized. I heard a potential client once claim, “Oh, this will be easy; our project is very platform,” only to find out that it was unlike any platform any of us had ever seen before! In addition, as technologies evolve, a CMO must keep current in order to have the latest offering available, yet must do so without wasting time and money on technological dead-ends.
Even more troubling to CMOs is the fact that they, like regulators, have seen many platforms. CMOs often have a very keen insight into the many different ways one can approach the same problem. In other words, the CMO may actually know a better way. Its ability to influence a client varies, of course, and it is difficult to discern if a client has deliberately chosen the platform, or if it evolved by default, but then again, the client might be open to improvements.
Although bound by confidentiality between clients, patterns in practices do emerge, and if you have seen enough platforms, you know that none is perfect, and each must sub-optimize something to achieve standardization. Common problems often have multiple solutions, and since a CMO is primarily driven to help the client succeed, knowledge of what works best in terms of equipment and facility may give the CMO significant insight into the limitations of a client’s platform.
The key to success is to adapt as necessary. In an ideal client-CMO relationship, each party will bring a wealth of knowledge and experience to the table. I have learned something from every project I have participated in, whether as a client or as a service provider. Being open to the possibilities of change, recognizing improvements, and even working together to define expectations for external providers can bring great benefits to the collaboration, and indeed to the industry. Vendors will respond to market demands, and two voices are stronger than one.
The possibility of change itself is not inherently bad, either. In fact, a process that performs well under a variety of production scenarios is inherently more robust, and provides greater assurance of consistency in the future. The more your process performs well under different conditions, the more likely it is to do so later. The biopharmaceutical production industry is far from fully mature, and improvements and innovations are taking place all the time. Ideally, a client-CMO relationship would enhance both organizations, and strengthen the fundamental platform on which a successful collaborative relationship is built.
Morrey Atkinson is chief scientific officer and vice president of R&D at Cook Pharmica, a bio-CDMO based in Bloomington, IN. Prior to joining Cook Pharmica, he spent nine years at Eli Lilly & Co., as both head of Biotechnology Manufacturing Sciences and Technology in Kinsale, Ireland and director of Bioprocess R&D in Indianapolis, IN. Having experience in both of the sponsor and provider areas, he has a unique perspective on the challenges that drug companies face, as well as the outsourcing services that support them. Morrey will occasionally discuss biopharma issues in this space from both of these viewpoints. To comment on this article or suggest a topic of interest, please contact him at morrey.atkinson@cookpharmica.com.
